In the ARTEMIS UC phase 2 trial, treatment with tulisokibart, an antibody targeting tumor necrosis factor-like cytokine 1A (TL1A), resulted in significantly higher remission rates during induction therapy for ulcerative colitis compared to placebo (Sands et al.). TL1A is a key pro-inflammatory cytokine with pro-fibrogenic properties, and its multifaceted mechanism of action may play an important role in the future treatment of inflammatory bowel disease. For this reason, several TL1A antibodies are currently being evaluated in phase 3 trials for the treatment of ulcerative colitis and Crohn’s disease. Patients with steroid-refractory acute severe ulcerative colitis are often given higher doses of infliximab at shorter intervals in order to optimize the therapeutic response. Now, this strategy has been called into question by the Australian PREDICT-UC trial, which found that a double dose of infliximab with shortened dosing intervals had no impact on clinical response or colectomy rates (Choy et al.).

Computer-aided detection (CADe) of polyps has been promoted in recent years as a key innovation for endoscopic colorectal screening. However, a multicenter trial found that incorporating CADe into colorectal screening resulted in only a minimal increase in the adenoma detection rate and rarely affected the recommended follow-up intervals, likely diminishing its overall added benefit (Sinonquel et al.). The efficacy of treatment with checkpoint inhibitors has been demonstrated in multiple treatment settings for microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer. In a phase 3 trial, first-line therapy with nivolumab plus ipilimumab in patients with metastatic disease significantly improved progression-free survival (72%) at 24 months compared to standard chemotherapy (14%) (Andre et al.).

Patients with pancreatic cancer continue to show poor responses to chemotherapy. A proof-of-concept trial investigated the use of organoids derived from pancreatic cancer biopsies to predict chemotherapy response. After cultivation of the organoids, potentially effective chemotherapy treatments were identified in 91% of patients. Targeted therapy resulted in better overall survival outcomes compared to standard therapy (Boilève et al.).

Progress has also been reported in liver cancer therapy. A French research group identified tumor DNA in the blood of individuals with hepatocellular carcinoma. Longitudinal analyses of mutations in the tumor material and the blood from the same individuals revealed that tumor-specific mutations in the circulation closely matched those in tumor tissue and the changes in mutation burden correlated with treatment response and disease stage (Campani et al.).

The clinical benefits of determining quantitative HBsAg in individuals with chronic hepatitis B virus infection are becoming increasingly evident. A Chinese study developed a predictive model that estimates the likelihood of HBsAg loss with high accuracy through biannual measurement of quantitative HBsAg in individuals undergoing nucleos(t)ide analogue therapy (Fan et al.).

The utility of transient elastography may also improve in the future. A European multicenter study involving more than 400 individuals with chronic liver disease found that spleen stiffness measurement combined with body mass index and platelet count identified clinically significant portal hypertension as efficiently as liver stiffness measurement. The combination of liver and spleen stiffness measurement with body mass index and platelet count even outperformed currently available diagnostic models (Jachs et al.).

We hope you find these articles, along with the other publications summarized in this issue, both stimulating and informative. We also aim for this selection to be valuable in your daily clinical practice and to address relevant questions.

Yours sincerely,
Peter Hasselblatt and Tobias Böttler
Department of Internal Medicine II, University Medical Center Freiburg (Germany)

Christoph Neumann-Haefelin

Peter Hasselblatt